B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation

Hyunkeun Song, Gabin Park, Yeong Seok Kim, Indo Hur, Hyunjin Kim, Jeoung Whan Ryu, Hyun Kyung Lee, Dae Ho Cho, In Hak Choi, Wang Jae Lee, Dae Young Hur

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29 Citations (Scopus)

Abstract

B7-H4 has an inhibitory effect on immune responses via the down-regulation of T cell-mediated immunity, but how the engagement of B7-H4 molecules by counter molecules affects the signaling mechanism of the B7-H4-expressing cells is poorly defined. In this study, we found that B7-H4 expression was enhanced on B cells infected with Epstein-Barr virus (EBV) and that triggering of these molecules induced apoptosis of EBV-transformed B cells. Engagement of B7-H4 initially increased intracellular level of ROS, which then induced the expression of FasL. Engagement of B7-H4 subsequently provoked Fas-mediated and caspase-dependent apoptosis in association with cytochrome c and AIF, and EndoG was released from the mitochondria on EBV-transformed B cells. These results suggest that B7-H4 may be a potential therapeutic target for EBV involved malignancy diseases.

Original languageEnglish
Pages (from-to)227-237
Number of pages11
JournalCancer letters
Volume266
Issue number2
DOIs
Publication statusPublished - 2008 Aug 8
Externally publishedYes

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Keywords

  • Apoptosis
  • B cell
  • B7-H4
  • EBV
  • Fas
  • FasL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Song, H., Park, G., Kim, Y. S., Hur, I., Kim, H., Ryu, J. W., Lee, H. K., Cho, D. H., Choi, I. H., Lee, W. J., & Hur, D. Y. (2008). B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation. Cancer letters, 266(2), 227-237. https://doi.org/10.1016/j.canlet.2008.02.067